Platelet transfusion is an often life-saving form of patient treatment, since platelets are required for normal hemostasis, i.e for bleedings from wounds to stop normally; on the other hand, platelets may appear in too small numbers due to certain diseases and/or treatments. Blood donors may be the source of platelet concentrates for transfusion in two principally different ways, one being conventional whole blood donation and the other being so called platelet apheresis by means of a blood cell separator.
With the objective to make the best possible use of the unique raw material, in modern transfusion medicine it is the routine worldwide that whole blood is separated into its main components, usually according to one of the systems first described by Professor Claes Homaan, M.D., Uppsala, Sweden. In these procedures platelets may be recovered either from the platelet rich plasma resulting from a first step of centrifugation, carried out at relatively few revolutions per minute, or from the so called buffy coat, which constitutes the top layer of blood particles after normal, harder centrifugation of the primary blood bag, in which case the supernatant plasma turns out to be virtually platelet-free.
Especially in Italy and in Sweden, a new important routine method has rapidly been established in order to satisfy the extremely great need for platelets in some hospitals, viz. so called pooling of 1-6 buffy coat preparations, including a small amount of accompanying erythrocytes and also a small volume of plasma, with the ensuing dilution with 250-300 ml of either standard saline solution or of a more complex solution containing carbohydrates and saline, followed by a final step of centrifugation low rotary speed for the elimination of erythrocytes and leukocytes from the platelet preparation.
Platelet apheresis is a procedure within transfusion medicine/blood banking, which has been well established for 10-15 years and which by use of a blood call separator makes it possible for one single donor in 60 to 90 minutes to put a full transfusion dosis of hemostatically active platelets to the disposition of a patient in need. This method of procurement has several advantages for the patient as compared with preparing a so to say pooled platelet concentrate from 4-8 whole blood units from conventional blood donation. Carried out professionally by means of blood cell separators of various kinds, platelet apheresis and similar, more frequently occurring plasmapheresis as plasma donation, are completely safe ventures.
However, platelet apheresis is an expensive procedure, particularly since the shelf-life of platelet concentrates--best stored at 20-24.degree. C. while mixed by rocking horizontally or rotation end over end at slow speed in special plastic bags permeable to oxygen and carbon dioxide--at present is approximately 5, at the most 7 days. The high costs are also caused by the fact that the often strongly variable demands, combined with the requirements for an adequate stock-pile of platelets for emergencies, provoke a great degree of loss from outdating (e.g. in Malmo, Sweden, at a yearly cost of approximately SEK 200,000).
It has recently been demonstrated that the shelf-life of platelet concentrates may be virtually doubled by one single stroke, carried out as the (next to) last step during the preparation of pooled buffy coat concentrates by including acetate into the diluting platelet additive solution, in other words, acetic acid as the salt thereof, neutral or slightly alkaline sodium acetate. Apparently, added acetate can be used as a physiological source of energy in the so called tricarboxylic acid cycle of platelets. This system for the conversion of energy, also called Kreb's Cycle after its discoverer, is found in all living cells.
However, at variance with most other cells (stored), platelets lack the enzyme system, which can transform glucose to acetate for introduction into the tricarboxylic acid cycle. Still, glucose is metabolized in a limited way, so called glycolysis the result of which is lactic acid, causing the pH of standard platelet concentrates from apheresis or whole blood to fall with a speed related, inter alia, to platelet number and concentration of bicarbonate. The latter is the most important buffer of plasma. Typically, within 6-8 days the pH of standard platelet concentrates have fallen to below 6.5 or below 6.2, where platelets rapidly loose hemostatic capacity and viability. As pointed out by F. Bertolino, S. Murphy, R. Rebulla and G. Sirchia (Transfusion 1992; 32: 152-156) acetate per se has no buffering capacity but when available to platelets during storage it has a pH-stabilizing affect, apparently because acetate is metabolized in the tricarboxylic acid cycle as acetic acid, oxidized all the way to carbon dioxide and water. In this way, acetate is consumed together with a proton, in other words an acidifying hydrogen ion. It may be derived either from carbonic acid, thus converted to buffering bicarbonate, or directly from lactic acid being converted to virtually nontoxic sodium lactate, the overall affect being that pH may stay approximately at pH 7 for more than 12 days, as reported by these authors and coinciding with our experience at the Blood Transfusion Centre of Malmo, Sweden. It has been stressed, inter alia by S. Holme (Blood Cells 1992; 18:421-430) that maintenance of the pH of platelet concentrates at approximately pH 7 is the singular most important in vitro characteristic of viable, hemostatically active stored platelets. In fact, apheresis platelets stored in citrate (ACD-A) plasma with acetate have proven repeatedly to normalize prolonged Ivy bleeding time 12 days after donation.
From the extensive use of acetate in intravenously applied preparations for fluid substitution and from the inclusion of significant amounts of acetic acid in everyday food it is apparent that (sodium) acetate is a completely nontoxic substance as long as it is not administered so as to produce clearly nonphysiological concentrations, e.g. as in acetate-based hemodialysis, or causing osmotic side effects and the like.
In fact, intravenous drip solutions containing 50 millimoles acetate (in addition to 100 millimoles chloride and 150 millimoles sodium ion, all this per litre), particularly when given intravenously in volumes of several litres, have physiological advantages over so called physiological saline solution in that the acid-base balance of the body is not tipped to the acid side (as shown by Professor Gosta Rooth of Lund, nowadays in Uppsala).
Platelet concentrates, after being prepared by apheresis or in any other way, may then be manipulated for the addition of acetate or other substances, the condition being that it can be done without contamination of the product, especially considering the risk of bacterial growth at the actual storage temperature, 20-24.degree. C. Also if that problem apparently can be solved today by application of expensive equipment for so called "mirror welding" of PVC tubing end to end (Haemonetics/Dupont Sterile Connecting Device SCD 312), or by preattachnent to the disposable kit of tubings, bags etc. for platelet apheresis there is the disadvantage of (concomitant) dilution of the plasma of platelet concentrates, which in turn appears to reduce the shelf-life of platelets.